Ligand-controlled palladium catalysis enables switch between mono- and di-arylation of primary aromatic amines with 2-halobenzothiazoles†
Herein, a wide range of mono- and di-arylated products were efficiently prepared from C–N coupling of 2-halobenzothiazoles and primary aromatic amines, and representative compounds 3b and 4b were further confirmed by X-ray crystallography. It was noteworthy that the di-arylated products, denoted as di(benzothiazolyl)amines, are new chemical entities which have not yet been reported. Moreover, the ligand-controlled protocol was extended to the synthesis of target molecules bearing a diphenyl ether or diphenyl amine scaffold. To our delight, several compounds exhibited good inhibitory activity against succinate-cytochrome c reductase (SCR), which revealed the practical application of this protocol. Notably, selective mono- and di-arylation could be switched simply by varying the ligand from Xantphos to a pyridine-functionalized N-heterocyclic carbene (NHC) ligand, and further investigations were carried out to elucidate the possible reason for this new finding.